title: Cutting Edge: CD1a tetramers and dextramers identify human lipopeptide-specific T cells ex vivo.
abstract: Human CD1a mediates foreign Ag recognition by a T cell clone, but the nature of possible TCR interactions with CD1a/lipid are unknown. After incubating CD1a with a mycobacterial lipopeptide Ag, dideoxymycobactin (DDM), we identified and measured binding to a recombinant TCR (TRAV3/ TRBV3-1, KD of ≈100 μM). Detection of ternary CD1a/lipid/TCR interactions enabled development of CD1a tetramers and CD1a multimers with carbohydrate backbones (dextramers), which specifically stained T cells using a mechanism that was dependent on the precise stereochemistry of the peptide backbone and was blocked with a soluble TCR. Furthermore, sorting of human T cells from unrelated tuberculosis patients for bright DDM-dextramer staining allowed recovery of T cells that were activated by CD1a and DDM. These studies demonstrate that the mechanism of T cell activation by lipopeptides occurs via ternary interactions of CD1a/Ag/TCR. Furthermore, these studies demonstrate the existence of lipopeptide-specific T cells in humans ex vivo.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Anne G
authors.initials: AG
authors.lastname: Kasmar
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
authors.forename: Kelly G
authors.initials: KG
authors.lastname: Magalhaes
authors.forename: David C
authors.initials: DC
authors.lastname: Young
authors.forename: Tan-Yun
authors.initials: TY
authors.lastname: Cheng
authors.forename: Marie T
authors.initials: MT
authors.lastname: Turner
authors.forename: Andre
authors.initials: A
authors.lastname: Schiefner
authors.forename: Ravi C
authors.initials: RC
authors.lastname: Kalathur
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Mugdha
authors.initials: M
authors.lastname: Bhati
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Richard W
authors.initials: RW
authors.lastname: Birkinshaw
authors.forename: Li L
authors.initials: LL
authors.lastname: Tan
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: John
authors.initials: J
authors.lastname: Shires
authors.forename: Søren
authors.initials: S
authors.lastname: Jakobsen
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D055666:Lipopeptides / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D010080:Oxazoles / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D055666:Lipopeptides; D010080:Oxazoles; D011948:Receptors, Antigen, T-Cell; C585579:dideoxymycobactin